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FBXW7
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Interpretation 2215
Tier 2
FBXW7
Variants
FBXW7 R393*
Primary Sites
Colon
Tumor Types
Adenocarcinoma
Interpretation

FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. mTOR is one of the substrates of FBXW7-mediated protein degradation, and loss of function of FBXW7 increases the levels of total and activated mTOR. Due to the disruption of the WD repeat domain, the FBXW7 R393* truncating mutation is predicted to lead to a loss of FBXW7 protein function. Preclinical data have suggested that inactivating mutations of FBXW7 could predict sensitivity to the mTOR inhibitor rapamycin; however, the clinical utility remains unknown. A single study has reported only limited activity in phase I trials using mTOR inhibitors in patient with advanced cancers including colorectal cancer.

Citations
  1. Uniprot.org
  2. Jardim DL, Wheler JJ, Hess K, et al. FBXW7 Mutations in Patients with Advanced Cancers: Clinical and Molecular Characteristics and Outcomes with mTOR Inhibitors. Li JJ, ed. PLoS ONE. 2014;9(2):e89388.
  3. Mao JH, Kim IJ, Wu D, Climent J, Kang HC, et al. (2008) FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 321: 1499--1502.
  4. Wang Y, Liu Y, Lu J, Zhang P, Wang Y, et al. (2013) Rapamycin inhibits FBXW7 loss-induced epithelial-mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells. Biochem Biophys Res Commun.
Last updated: 2018-04-18 14:41:45 UTC
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